{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T01:57:33Z","timestamp":1789178253694,"version":"build-2803163510"},"reference-count":22,"publisher":"Springer Science and Business Media LLC","issue":"5","license":[{"start":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T00:00:00Z","timestamp":1760400000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T00:00:00Z","timestamp":1760400000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Universit\u00e4tsklinikum des Saarlandes und Medizinische Fakult\u00e4t der Universit\u00e4t des Saarlandes"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Strahlenther Onkol"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Hemophagocytic lymphohistiocytosis (HLH) is a\u00a0life-threatening hyperinflammatory syndrome characterized by supramaximal immune activation. Although rare, HLH has been increasingly recognized as an immune-related adverse event in patients undergoing immune checkpoint inhibitor (ICI) therapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Case presentation<\/jats:title>\n                    <jats:p>We report the case of a\u00a0female patient treated with concomitant radio-chemo-immunotherapy for cervical cancer (according to the KEYNOTE-A18 trial). She developed HLH following a\u00a0single dose of pembrolizumab, presenting initially with immune-mediated pneumonitis and subsequently with fever, prolonged pancytopenia, and elevated inflammatory markers. After intensive diagnostics, broad-spectrum anti-infective treatment and granulocyte colony-stimulating factor (G-CSF) stimulation was started, without improvement. The diagnosis was finally made by HLH-2004 criteria, strongly indicated by an H\u2011score of 251 (&gt;\u202f99% probability of HLH). The HLH was successfully treated with corticosteroids alone.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This case highlights the importance of early recognition and aggressive management of HLH secondary to immunotherapy, particularly in patients presenting with unexplained fever, G\u2011CSF-refractory cytopenia, and hyperferritinemia.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00066-025-02478-w","type":"journal-article","created":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T23:46:59Z","timestamp":1760399219000},"page":"539-543","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Hemophagocytic lymphohistiocytosis induced by radio-chemo-immunotherapy: a\u00a0case report"],"prefix":"10.1007","volume":"202","author":[{"given":"Bryan","family":"Salazar-Zuniga","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorenz","family":"Thurner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobias","family":"Mohr","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philipp","family":"Staber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Hecht","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Octavian","family":"Fleser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,10,14]]},"reference":[{"issue":"2","key":"2478_CR1","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1016\/S0889-8588(05)70520-7","volume":"12","author":"JI Henter","year":"1998","unstructured":"Henter\u00a0JI, Aric\u00f2\u00a0M, Elinder\u00a0G et\u00a0al (1998) Familial hemophagocytic lymphohistiocytosis (primary HLH). Hematol Oncol Clin North Am 12(2):417\u2013433","journal-title":"Hematol Oncol Clin North Am"},{"issue":"3","key":"2478_CR2","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1016\/j.cytogfr.2014.10.001","volume":"26","author":"E Brisse","year":"2015","unstructured":"Brisse\u00a0E, Wouters\u00a0CH, Matthys\u00a0P (2015) Hemophagocytic lymphohistiocytosis (HLH): a\u00a0heterogeneous spectrum of cytokine-driven immune disorders. Cytokine Growth Factor Rev 26(3):263\u2013280","journal-title":"Cytokine Growth Factor Rev"},{"issue":"9927","key":"2478_CR3","doi-asserted-by":"publisher","first-page":"1503","DOI":"10.1016\/S0140-6736(13)61048-X","volume":"383","author":"M Ramos-Casals","year":"2014","unstructured":"Ramos-Casals\u00a0M, Brito-Zer\u00f3n\u00a0P, L\u00f3pez-Guillermo\u00a0A, Khamashta\u00a0MA, Bosch\u00a0X (2014) Adult haemophagocytic syndrome. Lancet 383(9927):1503\u20131516","journal-title":"Lancet"},{"issue":"2","key":"2478_CR4","doi-asserted-by":"publisher","first-page":"364","DOI":"10.1002\/eji.201646686","volume":"47","author":"S Ammann","year":"2017","unstructured":"Ammann\u00a0S, Lehmberg\u00a0K, zur Stadt\u00a0U et\u00a0al (2017) Primary and secondary hemophagocytic lymphohistiocytosis have different patterns of T\u2011cell activation, differentiation and repertoire. Eur J Immunol 47(2):364\u2013373","journal-title":"Eur J Immunol"},{"issue":"5","key":"2478_CR5","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1093\/intimm\/dxy012","volume":"30","author":"GS Schulert","year":"2018","unstructured":"Schulert\u00a0GS, Canna\u00a0SW (2018) Convergent pathways of the hyperferritinemic syndromes. Int Immunol 30(5):195\u2013203","journal-title":"Int Immunol"},{"issue":"6","key":"2478_CR6","doi-asserted-by":"publisher","first-page":"1227","DOI":"10.1002\/pbc.21423","volume":"50","author":"CE Allen","year":"2008","unstructured":"Allen\u00a0CE, Yu\u00a0X, Kozinetz\u00a0CA, McClain\u00a0KL (2008) Highly elevated ferritin levels and the diagnosis of hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer 50(6):1227\u20131235","journal-title":"Pediatr Blood Cancer"},{"issue":"23","key":"2478_CR7","doi-asserted-by":"publisher","first-page":"2465","DOI":"10.1182\/blood.2018894618","volume":"133","author":"P La Ros\u00e9e","year":"2019","unstructured":"La Ros\u00e9e\u00a0P, Horne\u00a0A, Hines\u00a0M et\u00a0al (2019) Recommendations for the management of hemophagocytic lymphohistiocytosis in adults. Blood 133(23):2465\u20132477. https:\/\/doi.org\/10.1182\/blood.2018894618","journal-title":"Blood"},{"issue":"9","key":"2478_CR8","doi-asserted-by":"publisher","first-page":"2613","DOI":"10.1002\/art.38690","volume":"66","author":"L Fardet","year":"2014","unstructured":"Fardet\u00a0L, Galicier\u00a0L, Lambotte\u00a0O et\u00a0al (2014) Development and validation of the HScore, a\u00a0score for the diagnosis of reactive hemophagocytic syndrome. Arthritis Rheumatol 66(9):2613\u20132620","journal-title":"Arthritis Rheumatol"},{"issue":"11","key":"2478_CR9","doi-asserted-by":"publisher","first-page":"1731","DOI":"10.1002\/cncr.33477","volume":"127","author":"JC Lee","year":"2021","unstructured":"Lee\u00a0JC, Logan\u00a0AC (2021) Diagnosis and management of adult malignancy-associated hemophagocytic lymphohistiocytosis. Cancer 127(11):1731\u20131741. https:\/\/doi.org\/10.1002\/cncr.33477","journal-title":"Cancer"},{"key":"2478_CR10","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.30826","author":"N Daver","year":"2017","unstructured":"Daver\u00a0N, McClain\u00a0K, Allen\u00a0CE et\u00a0al (2017) A\u00a0consensus review on malignancy associated hemophagocytic lymphohistiocytosis in adults. Cancer. https:\/\/doi.org\/10.1002\/cncr.30826","journal-title":"Cancer"},{"key":"2478_CR11","doi-asserted-by":"publisher","first-page":"8111","DOI":"10.2147\/IJGM.S388880","volume":"15","author":"H Yildiz","year":"2022","unstructured":"Yildiz\u00a0H, Castanares-Zapatero\u00a0D, d\u2019Abadie\u00a0P, Bailly\u00a0S, Yombi\u00a0JC (2022) Hemophagocytic lymphohistiocytosis in adults: a\u00a0retrospective in a\u00a0belgian teaching hospital. Int J Gen Med 15:8111\u20138120","journal-title":"Int J Gen Med"},{"issue":"1","key":"2478_CR12","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1532\/IJH97.07012","volume":"86","author":"E Ishii","year":"2007","unstructured":"Ishii\u00a0E, Ohga\u00a0S, Imashuku\u00a0S et\u00a0al (2007) Nationwide survey of hemophagocytic lymphohistiocytosis in Japan. Int J Hematol 86(1):58\u201365","journal-title":"Int J Hematol"},{"key":"2478_CR13","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1186\/s40425-018-0365-3","volume":"6","author":"M Sadaat","year":"2018","unstructured":"Sadaat\u00a0M, Jang\u00a0S (2018) Hemophagocytic lymphohistiocytosis with immunotherapy: brief review and case report. J\u00a0Immunother Cancer 6:49","journal-title":"J Immunother Cancer"},{"key":"2478_CR14","doi-asserted-by":"publisher","first-page":"2960","DOI":"10.21037\/tcr-22-154","volume":"11","author":"Y Wei","year":"2022","unstructured":"Wei\u00a0Y, He\u00a0W, Sun\u00a0W et\u00a0al (2022) Hemophagocytic lymphohistiocytosis in two patients following treatment with pembrolizumab: two case reports and a\u00a0literature review. Transl Cancer Res 11:2960\u20132966","journal-title":"Transl Cancer Res"},{"key":"2478_CR15","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1016\/j.ejca.2017.02.016","volume":"77","author":"N Malissen","year":"2017","unstructured":"Malissen\u00a0N, Lacotte\u00a0J, Du-Thanh\u00a0A et\u00a0al (2017) Macrophage activation syndrome: a\u00a0new complication of checkpoint inhibitors. Eur J Cancer 77:88\u201389","journal-title":"Eur J Cancer"},{"issue":"4","key":"2478_CR16","doi-asserted-by":"publisher","first-page":"142","DOI":"10.14740\/jh1033","volume":"11","author":"R Marar","year":"2022","unstructured":"Marar\u00a0R, Prathivadhi-Bhayankaram\u00a0S, Krishnan\u00a0M (2022) Immune checkpoint inhibitor-induced hemophagocytic lymphohistiocytosis in a\u00a0patient with squamous cell carcinoma. J\u00a0Hematol 11(4):142\u2013147","journal-title":"J Hematol"},{"issue":"26","key":"2478_CR17","doi-asserted-by":"publisher","first-page":"5154","DOI":"10.1182\/blood-2013-02-485623","volume":"121","author":"DT Teachey","year":"2013","unstructured":"Teachey\u00a0DT, Rheingold\u00a0SR, Maude\u00a0SL et\u00a0al (2013) Cytokine release syndrome after blinatumomab treatment related to abnormal macrophage activation and ameliorated with cytokine-directed therapy. Blood 121(26):5154\u20135157","journal-title":"Blood"},{"key":"2478_CR18","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1186\/s40425-019-0598-9","volume":"7","author":"R Noseda","year":"2019","unstructured":"Noseda\u00a0R, Bertoli\u00a0R, M\u00fcller\u00a0L, Ceschi\u00a0A (2019) Haemophagocytic lymphohistiocytosis in patients treated with immune checkpoint inhibitors: analysis of WHO global database of individual case safety reports. J\u00a0Immunother Cancer 7:117","journal-title":"J Immunother Cancer"},{"issue":"1","key":"2478_CR19","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1186\/s40425-018-0384-0","volume":"6","author":"A Hantel","year":"2018","unstructured":"Hantel\u00a0A, Gabster\u00a0B, Cheng\u00a0JX, Golomb\u00a0H, Gajewski\u00a0TF (2018) Severe hemophagocytic lymphohistiocytosis in a\u00a0melanoma patient treated with ipilimumab, nivolumab. J\u00a0Immunother Cancer 6(1):73","journal-title":"J Immunother Cancer"},{"key":"2478_CR20","doi-asserted-by":"publisher","first-page":"e000604","DOI":"10.1136\/jitc-2020-000604","volume":"8","author":"J Haanen","year":"2020","unstructured":"Haanen\u00a0J, Ernstoff\u00a0M, Wang\u00a0Y et\u00a0al (2020) Rechallenge patients with immune checkpoint inhibitors following severe immune-related adverse events: review of the literature and suggested prophylactic strategy. J\u00a0Immunother Cancer 8:e604. https:\/\/doi.org\/10.1136\/jitc-2020-000604","journal-title":"J Immunother Cancer"},{"issue":"12","key":"2478_CR21","doi-asserted-by":"publisher","first-page":"1217","DOI":"10.1016\/j.annonc.2022.07.001","volume":"33","author":"J Haanen","year":"2022","unstructured":"Haanen\u00a0J, Obeid\u00a0M, Spain\u00a0L et\u00a0al (2022) Management of toxicities from immunotherapy: ESMO clinical practice guideline for diagnosis, treatment and follow-up. Ann Oncol 33(12):1217\u20131238. https:\/\/doi.org\/10.1016\/j.annonc.2022.07.001","journal-title":"Ann Oncol"},{"issue":"12","key":"2478_CR22","doi-asserted-by":"publisher","first-page":"e2245596","DOI":"10.1001\/jamanetworkopen.2022.45596","volume":"5","author":"AS Watson","year":"2022","unstructured":"Watson\u00a0AS, Goutam\u00a0S, Stukalin\u00a0I et\u00a0al (2022) Association of immune-related adverse events, hospitalization, and therapy resumption with survival among patients with metastatic melanoma receiving single-agent or combination immunotherapy. JAMA Netw Open 5(12):e2245596. https:\/\/doi.org\/10.1001\/jamanetworkopen.2022.45596","journal-title":"JAMA Netw Open"}],"container-title":["Strahlentherapie und Onkologie"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00066-025-02478-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00066-025-02478-w","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00066-025-02478-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T11:42:14Z","timestamp":1777030934000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00066-025-02478-w"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,14]]},"references-count":22,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2026,5]]}},"alternative-id":["2478"],"URL":"https:\/\/doi.org\/10.1007\/s00066-025-02478-w","relation":{},"ISSN":["0179-7158","1439-099X"],"issn-type":[{"value":"0179-7158","type":"print"},{"value":"1439-099X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,14]]},"assertion":[{"value":"6 July 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 September 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 October 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"B.\u00a0Salazar-Zuniga, L.\u00a0Thurner, T.\u00a0Mohr, P.\u00a0Staber, M.\u00a0Hecht, and O.\u00a0Fleser declare that they have no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}